1. Field of the Invention
This invention relates to novel derivatives of quinolopyran-4-one-2-carboxylic acid esters and to their uses as medical drugs.
These novel compounds are useful as antiallergic remedies for asthma or antasthmatics, and can be orally administered. Moreover, they have long duration of action.
2. Prior Art
Cox et al have reported that disodium cromoglycate developed recently is effective for allergic asthma [Adv. in Drug Res. 5, 115 (1970)]. This compound is considered to exhibit its effectiveness by inhibiting the release of chemical mediators from mast cells which have resulted from the antigen-antibody reaction caused by the reagin antibody. This compound, however, is disadvantageous in that it cannot be absorbed via oral administration and has a short duration of action.
On the other hand, the present inventors have provided the derivatives of quinolopyran-4-one-2-carboxylic acids which are similar to the compounds of the present invention represented by the general formula [I], which will be described in detail hereinafter, and found that the derivatives are useful as antiallergic remedies for asthma. See, Japanese Unexamined Patent Publication Nos. 17,498/77 and 109,000/77, which are equivalent to, e.g., U.S. Pat. No. 4,086,349.
In the present invention, it is essential that the present compounds be esters of the quinolopyran-4-one-2-carboxylic acids with the specified alcohols (R--OH), wherein the definition of R is given below with respect to the general formula [I]. The ester derivatives of the acids wherein R of the alcohol is a C.sub.1 to C.sub.5 alkyl, phenyl and benzyl are disclosed in the above-mentioned Unexamined Patent Publication No. 17,498/77. In the specification, methyl, ethyl and n-butyl alcohols are given as specific examples of C.sub.1 to C.sub.5 alkyls. However, neither physical property data nor pharmacological data are given with respect to these five species of esters. (The invention disclosed in the Unexamined Patent Publication No. 17,498/77 is described as a process for preparation, and thus both the physical property data and the pharmacological data are not shown therein.) Moreover, while it is disclosed in the Unexamined Publication that the compounds may be in the form of esters as well as acids and salts, the specification is also silent as to specific dosages for oral administration when the compounds are in the form of esters, although the general dosages for oral administration of these compounds are given.
In the Unexamined Patent Publication No. 109,000/77, the antiallergic remedies for asthma comprising the quinolopyran-4-one-2-carboxylic acid derivatives or the salts thereof and the dosages for oral administration thereof are described.
The derivatives of quinolopyran-4-one-2-carboxylic acids, which have free carboxylic groups, may be thus administered orally. These compounds themselves, however, are inactivated in the stomach and are required to be in the form of entric drugs to prevent the inactivation in the stomach and to commence absorption in the duodenum. Such methods of administration are practically difficult, and the effectiveness will fluctuate from person to person.
Thus, in the prior inventions by the present inventors, these compounds in the form of free acids may be said to have problems of oral administration thereof.